Sector-Based Regression Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography.

Purpose: This cross-sectional study aimed to investigate the sectoral variance of optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters across eyes with varying degrees of refractive error. Methods: Healthy participants, including individuals with axial ametropia, enrolled in the Hong Kong FAMILY cohort were imaged using the Avanti/AngioVue OCT/OCTA system. The OCT and OCTA parameters obtained include peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), and macular ganglion cell complex thickness (GCCT). Sectoral measurements of NFLT, NFLP-CD, and GCCT were based on sectors and hemispheres. Results: A total of 1339 eyes from 791 participants were stratified based on spherical equivalent refraction: high myopia (<-6 D), low myopia (-6 D to -1 D), emmetropia (-1 D to 1 D), and hyperopia (>1 D). Multivariable broken stick regression models, accounting for age, sex, and signal strength, showed that all NFLT sectors except temporally, the inferior GCCT hemisphere, and half of the NFLP-CD sectors were more affected by ametropia-related covariates than the corresponding global parameters. As expected, the false-positive rates in those sectors were elevated. Finally, sector-specific axial length (AL) and spherical equivalent (SE) adjustments helped reduce the elevated false-positive rates. Conclusions: The effect of optical magnification is even more prominent among sectors than the global parameters. AL- and SE-based adjustments should be individualized to each sector to mitigate this magnification bias effectively. Translational Relevance: Identifying sectoral differences among diagnostic parameters and adopting these sector-based adjustments into commercial OCT systems will hopefully reduce false-positive rates related to refractive error.

Regression-Based Strategies to Reduce Refractive Error-Associated Glaucoma Diagnostic Bias When Using OCT and OCT Angiography.

Purpose: The purpose of this study was to correct refractive error-associated bias in optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters. Methods: OCT and OCTA imaging were obtained from participants in the Hong Kong FAMILY cohort. The Avanti/AngioVue OCT/OCTA system was used to measure the peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), macular ganglion cell complex thickness (GCCT), and macular superficial vascular complex vascular density (SVC-VD). Healthy eyes, including ones with axial ametropia, were enrolled for analysis. Results: A total of 1346 eyes from 792 participants were divided into 4 subgroups: high myopia (<-6D), low myopia (-6D to -1D), emmetropia (-1D to 1D), and hyperopia (>1D). After accounting for age, sex, and signal strength, multivariable regression showed strong dependence in most models for NFLT, GCCT, and NFLP-CD on axial eye length (AL), spherical equivalent (SE) refraction, and apparent optic disc diameter (DD). Optical analysis indicated that AL-related transverse optical magnification variations predominated over anatomic variations and were responsible for these trends. Compared to the emmetropic group, the false positive rates were significantly (Chi-square test P < 0.003) elevated in both myopia groups for NFLT, NFLP-CD, and GCCT. Regression-based adjustment of these diagnostic parameters with AL or SE significantly (McNemar test P < 0.03) reduced the elevated false positive rates. Conclusions: Myopic eyes are biased to have lower NFLT, GCCT, and NFLP-CD measurements. AL- and SE-based adjustments were effective in mitigating this bias. Translational Relevance: Adoption of these adjustments into commercial OCT systems may reduce false positive rates related to refractive error.

Effectiveness of Microcurrent Stimulation in Preserving Retinal Function of Blind Leading Retinal Degeneration and Optic Neuropathy: A Systematic Review.

OBJECTIVES: To systematically identify and summarize the effectiveness and the parameters of electrical stimulation (ES) for the preservation of visual function in major retinal degeneration and optic neuropathy. MATERIALS AND METHODS: A systematic review of clinical studies, using ES therapy in patients with blind leading retinal degenerations, including retinitis pigmentosa (RP), age-related macular degeneration (AMD), glaucoma, retinal vein occlusion (RVO), retinal artery occlusion (RAO), and optic neuropathy was conducted. PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant interventional studies including randomized controlled trials (RCTs) and observational studies. RESULTS: A total of 10 RCTs and 15 observational studies were included. Transcorneal ES (TcES), transpalpebral ES (TpES), transdermal ES (TdES), and repetitive transorbital alternating current stimulation (rtACS) were used for the treatment of the patients. ES using 20 Hz biphasic pulses with current strength at 150%-200% of individual electrical phosphene threshold (EPT) for RP patients showed improved retinal function detected by visual acuity (VA), visual field (VF), or electrical retinal graphs (ERG). rtACS on patients with optic neuropathy showed significant preservation of VA and VF. Clinical studies on AMD, RAO, and glaucoma indicated promising protective effects of ES on the visual function, though the amount of evidence is limited. CONCLUSIONS: ES treatment has promising therapeutic effects on RP and optic neuropathy. More large-scale RCT studies should be conducted to elucidate the potential of ES, especially on AMD, RAO, and glaucoma. A comparison of the effects by different ES methods in the same disease populations is still lacking. Parameters of the electric current and sensitive detection method should be optimized for the evaluation of ES treatment effects in future studies.

Does the COVID-19 Pandemic Spell the End for the Direct Ophthalmoscope?

Despite advances in ophthalmic diagnostics, the direct ophthalmoscope remains a key clinical skill taught to medical students and is the tool of choice for retina examination among non-ophthalmic physicians. However, in recent years viable alternatives have become available. The coronavirus disease 2019 (COVID-19) pandemic has forced a major re-thinking in medical education worldwide. In this commentary, we examined the current merits and limitations of the direct ophthalmoscope in both the clinical sense and in the context of infection control. Furthermore, we compared the direct ophthalmoscope with alternatives, including commercially available portable non-mydriatic fundus cameras, that would allow a change in focus during ophthalmic teaching. We concluded that the latter will better prepare our medical students for the age of telemedicine and deep-learning systems. While the COVID-19 pandemic will not be the sole reason for the 'death' of the direct ophthalmoscope, the global situation will inevitably serve to expedite long overdue changes in our teaching of ophthalmic skills to non-ophthalmic physicians.

A Serial Cross-Sectional Analysis of the Prevalence, Risk Factors and Geographic Variations of Reduced Visual Acuity in Primary and Secondary Students from 2000 to 2017 in Hong Kong.

Background: We would like to investigate the prevalence trend, potential risk factors and geographic features of reduced visual acuity (VA) in primary and secondary schoolchildren of Hong Kong. Methods: This was a serial cross-sectional study using historical data of schoolchildren aged 6 to 15 years from the annual health checks conducted at Student Health Service Centers across Hong Kong, for the school years of 2000/2001 to 2016/2017. Results: The prevalence of reduced VA increased from 49.23% (95% CI, 48.99-49.47) in 2000/2001 to 54.34% (95% CI, 54.10-54.58) in 2011/2012 but decreased to 51.42% (95% CI, 51.17-51.66) in 2016/2017. Girls were less susceptible than boys at age 6-7 (and in grade primary 1-2), but more susceptible at older ages. The prevalence in junior grades increased while the risk effect of grade reduced over the past 17 years. Geographic variation on the risk for reduced VA existed and spatial autocorrelation was positive. The difference in prevalence of reduced VA between Hong Kong and mainland China has decreased in recent years. Cross-border students living in mainland China were associated with a lower risk for reduced VA. Conclusions: Further study was proposed to investigate the environmental association between students living in and outside Hong Kong with the prevalence of reduced VA. Multi-level research should also be conducted to investigate the influence of compositional and contextual factors on the prevalence of reduced VA.

Phacoemulsification Versus Phacotrabeculectomy in Primary Angle-closure Glaucoma With Cataract: Long-Term Clinical Outcomes.

PRECIS: Phacotrabeculectomy was more effective in reducing intraocular pressure (IOP) and glaucoma drugs than phacoemulsification alone in primary angle-closure glaucoma (PACG) eyes with cataract but was associated with more postoperative complications, up to 5 years after surgery. PURPOSE: The purpose of this study was to compare long-term clinical outcomes of phacoemulsification versus phacotrabeculectomy in PACG eyes with cataract. PATIENTS AND METHODS: The 2 initial prospective randomized controlled trials recruited PACG eyes with cataract using the same criteria and randomized these eyes to receiving either phacoemulsification or phacotrabeculectomy. Clinical data up to 5 years of follow-up were pooled for retrospective analysis. RESULTS: Clinical data of 35 patients in the phacoemulsification group and 44 patients in the phacotrabeculectomy group were analyzed. At 5 years after surgery, the mean IOP was decreased by 20.7% and 29.5% from before surgery to 5 years after phacoemulsification and phacotrabeculectomy, respectively (P<0.001 for both groups). Phacotrabeculectomy was significantly more effective than phacoemulsification in reducing IOP up to 5 years after surgery (P<0.001). At 5 years, the mean number of glaucoma drugs required±1 SD was 1.6±1.2 in the phacoemulsification group, and 0.7±1.0 in the phacotrabeculectomy group (P=0.004). Phacotrabeculectomy was associated with more postoperative complications than phacoemulsification up to 5 years (25 complications in the phacotrabeculectomy group versus 6 in the phacoemulsification group, P<0.001). CONCLUSIONS: Phacoemulsification alone reduces IOP and the need for glaucoma drugs in PACG eyes with cataracts for up to 5 years. Phacotrabeculectomy was more effective in reducing IOP and glaucoma drugs than phacoemulsification alone but was associated with more postoperative complications, up to 5 years after surgery.

Macular Vessel Density Measured With Optical Coherence Tomography Angiography and Its Associations in a Large Population-Based Study.

Purpose: We investigate macular perfusion and the systemic and ocular associations in a population-based setting. Methods: In this cross-sectional study, 2018 adults residing in Hong Kong underwent detailed ophthalmic examinations after consenting to participate. Macular perfusion was measured with optical coherence tomography angiography (OCTA) using the split-spectrum amplitude decorrelation angiography algorithm. The parafoveal flow index and vessel area density were quantified using automated custom-built software. Results: Of the 2018 participants, the OCTA measurements were available for 1940, and 1631 (84.1%) had good quality scans. The right eyes of these 1631 participants (43.1% men) were included for final analysis. Mean age was 49.8 years (range, 18-92 years). Mean global macular vessel density was 47.3% and 55.1% for the superficial and deep retinal layers, respectively. In multivariate analysis, lower superficial vessel density remained significantly associated with lower signal strength index (SSI; P < 0.001, standardized ß = 0.607) and male sex (P < 0.001, ß = 0.162), and borderline associated with older age (P = 0.09, ß = -0.045) and longer axial length (AL; P = 0.09, ß = -0.037), while lower deep layer vessel density was significantly associated with lower SSI (P < 0.001, standardized ß = 0.667), longer AL (P < 0.001, ß = -0.097), and higher creatinine (P < 0.001, ß = -0.072). Conclusions: This large population-based study provided normative OCTA data of macular vessel density and demonstrated that a lower superficial retinal vessel density was significantly associated with lower SSI and male sex, while a lower deep layer retinal vessel density was significantly associated with lower SSI, longer AL, and higher level of creatinine. These associations must be considered when interpreting clinical quantitative OCTA data.

Exophthalmometry values in the Hong Kong Chinese adult population from a population-based study.

This study aims to establish the range of exophthalmometry values (EV) in the adult Hong Kong (HK) Chinese population, its relationship with various anthropometric parameters, and to compare it with the EV in different ethnic groups.About 1485 adult HK Chinese were drawn from a random sample from the community-based FAMILY Cohort. Participants were interviewed, and comprehensive ophthalmological assessments were conducted. EV was measured using the Hertel's exophthalmometer.EV of both eyes from 630 male (42.4%) and 855 female (57.6%) participants, mean age 54 ±â€Š17.2 and 52 ±â€Š16 respectively were analyzed. The mean EV were found to be 15.3 ±â€Š2.8 mm in the right eye, 15.2 ±â€Š2.9 mm in the left eye for men and 14.4 ±â€Š2.7 mm in the right eye, 14.3 ±â€Š2.7 mm in the left eye for women. There were no differences in the EV between right and left eyes (P > .05). Men had significantly higher EV than women (P < .05) and age was found to be negatively correlated to EV (P < .05). Body height (r = 0.20), weight (r = 0.25), waist (r = 0.11), hip circumference (r = 0.15), body mass index (r = 0.17), interpupillary distance (r = 0.54), and axial length (AL) (r = 0.20) were all found to have statistically significant positive correlations with EV (P < .01). Spherical equivalent was found to have statistically significant negative correlation with EV (P < .01).Our study provides normative data on EV in the HK Chinese population. Height, weight, interpupillary distance, waist, hip circumference, and AL had positive correlations with EV. Spherical equivalent had negative correlation with EV. There was no significant difference in EV between the right and left eye. Age and gender had significant effect on EV.

Prospective study on a novel treatment for leaking cystic bleb: Efficacy and safety of collagen crosslinking.

IMPORTANCE: Management of cystic bleb leak is difficult. It would be essential to look for a method to strengthen the original pathological conjunctiva and reverse bleb leak. BACKGROUND: To evaluate the long-term efficacy and safety of collagen crosslinking in patients with leaking cystic bleb. DESIGN: Prospective interventional case series at a university-based hospital. PARTICIPANTS: Twelve eyes in 12 subjects with late-onset bleb leak from cystic bleb, without indications for prompt surgical interventions were included. METHODS: The subjects underwent crosslinking with 0.1% riboflavin application to bleb surface, followed by ultraviolet irradiation for 30 minutes. The subjects were followed up at baseline and at 1 week, 1 month, 3 months, 6 months post-treatment and then every 6 months afterwards. MAIN OUTCOME MEASURES: Interval from treatment to cessation of bleb leak, recurrence rate of bleb leak and side effects of treatment. RESULTS: The mean follow-up after crosslinking was 29.33 ± 12.45 months. Bleb leak subsided in 11 (92%) of 12 patients after a single session of crosslinking, after 1 to 8 weeks (median 3 weeks). Time to leak cessation was significantly correlated with the number of prior glaucoma interventions (R = .71, P = .014). Bleb wall at 3 months was significantly thicker than at baseline (0.70 ± 0.67 vs 0.81 ± 0.62 mm, P = .008). None of the patients experienced any complications. CONCLUSIONS AND RELEVANCE: Crosslinking achieves resolution of cystic bleb leak which lasts for at least 12 months, without the need of subsequent surgical interventions. Crosslinking is a simple, non-invasive treatment for bleb leak. It aims to restore the integrity of conjunctiva.

Systematic Review on Therapeutic Strategies to Minimize Corneal Stromal Scarring After Injury.

OBJECTIVES: To evaluate recent studies on available and experimental therapies in preventing or minimizing corneal stromal scarring after injury. METHODS: We performed an Entrez PubMed literature search using keywords "cornea," "scarring," "haze," "opacity," "ulcer," "treatments," "therapies," "treatment complications," and "pathophysiology" resulting in 390 articles of which 12 were analyzed after filtering, based on English language and publication within 8 years, and curation for relevance by the authors. RESULTS: The 12 articles selected included four randomized control trials (RCTs) (two were double-blinded placebo-controlled RCTs, one was a prospective partially masked RCT, and one was an open-label RCT), two retrospective observational studies, and six laboratory-based studies including two studies having in vivo and in vitro experiments, one was in vivo study, one was ex vivo study, and the last two were in vitro studies. The current mainstay for preventing or minimizing corneal scarring involves the use of topical corticosteroids and local application of mitomycin C. However, supportive evidence for their use in clinical practice from well-designed RCTs is lacking. Laboratory studies on topical rosiglitazone therapy, vitamin C prophylaxis, gene therapy, and stem cell therapy have shown promising results but have yet to be translated to clinical research. CONCLUSION: There is a need for more robust randomized controlled trials to support treatments using topical corticosteroids and mitomycin C. Furthermore, their clinical efficacy and safety profile should be compared with new treatments that have shown promising results in the laboratory setting. Ultimately, the goal should be to personalize cornea scarring treatment according to the most effective treatment for the specific underlying pathology.

Optic neuritis as the initial clinical presentation of limbic encephalitis: a case report.

BACKGROUND: Limbic encephalitis is characterized by rapid onset of working memory deficit, mood changes, and often seizures. The condition has a strong paraneoplastic association, but not all cases are invariably due to tumors. CASE PRESENTATION: We present a case of limbic encephalitis in a Chinese patient who initially presented to our hospital with optic neuritis and no other neurological symptoms. The diagnosis was made radiologically, and cognitive and neurological symptoms did not occur until 5 months later. Extensive investigations for autoimmune, infective, and neoplastic causes were all negative. A working diagnosis of paraneoplastic neurological syndrome was made, and the patient is being managed with high-dose steroid therapy according to the Optic Neuritis Treatment Trial protocol during relapses, as well as with tumor surveillance. CONCLUSIONS: This case highlights ocular symptoms as important clues for diagnosing neurological diseases, as well as autoimmune encephalitis as an important differential diagnosis in the management of "idiopathic" optic neuritis in the Chinese population.

Early epithelial complications of accelerated trans-epithelial corneal crosslinking in treatment of keratoconus: a case series.

BACKGROUND: To report a case series of early postoperative complications following combined accelerated corneal crosslinking (CXL) and trans-epithelial technique in keratoconus. CASE PRESENTATIONS: Eleven eyes underwent accelerated trans-epithelial CXL (18 mW/cm2 for 5 min). Seven eyes (64%) developed complications in the first week postoperatively. Five eyes had large epithelial defects, and two eyes were complicated with diffuse punctate epithelial erosions. Early transient stromal haze was seen in eyes with epithelial complications. Anterior segment optical coherence tomography showed a faint demarcation line in six eyes (55%) with epithelial complications. CONCLUSION: A significant number of eyes developed epithelial complications shortly after combined accelerated trans-epithelial CXL, which defeated the benefits of leaving the epithelium intact.

A cross-sectional comparative study on chronic ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis in Chinese eyes: a 15-year case series.

PURPOSE: To compare the chronic ocular manifestations in Stevens-Johnson syndrome and toxic epidermal necrolysis patients from a 15-year cohort. METHODS: All SJS and TEN patients admitted to our burn intensive care unit between 1999 and 2014 were invited for assessment. Slit-lamp examination was performed, and ocular condition was graded according to the Sotozono scoring System, which depended on the extent of cornea, conjunctiva and lid involvement. Tear osmolarity was also measured. RESULTS: A total of 18 SJS and 4 TEN cases with an average of 92 and 135 months from disease onset were included. The average age of onset was 46.4 ± 16.6 in SJS and 43.5 ± 19.3 in TEN patients. The LogMAR visual acuity was 0.209 ± 0.591 in SJS and 0.489 ± 0.688 in TEN patients (p = 0.048). The average total Sotozono score was 3.75 ± 7.32 in SJS and 6.88 ± 9.49 in TEN (p = 0.358). Neither the age of onset (p = 0.787), length of follow-up (p = 0.256) nor disease type (SJS vs TEN, p = 0.188) predicted the Sotozono score. There was a statistically significant correlation between Sotozono score and LogMAR VA (r s = 0.437, p = 0.003). CONCLUSION: The average total Sotozono score was higher in the TEN group than in the SJS group, but the difference was not statistically significant. Nevertheless, the score correlated with the visual acuity which was statistically worse in the TEN group.

Predictability and stability of laser-assisted subepithelial keratectomy with mitomycin C for the correction of high myopia.

The purpose of this study was to evaluate the predictability and stability of laser-assisted subepithelial keratectomy (LASEK) with mitomycin C (MMC) in correction of high myopia (≤-6.0 diopters [D]) as compared to low-to-moderate myopia (>-6.0 D).This is a retrospective, comparative, cohort study which included 43 eyes of 43 consecutive patients who underwent LASEK with MMC in a private hospital in Hong Kong by a single surgeon. Twenty-five eyes had high myopia (mean spherical equivalent [SE] = -8.53 ±â€Š1.82 D) and 18 eyes had low-to-moderate myopia (mean SE = -3.99 ±â€Š1.37 D) before surgery.In terms of refractive predictability, mean SE was significantly better in eyes with preoperative low-to-moderate myopia than high myopia at 6 months (0.04 ±â€Š0.23 vs 0.31 ±â€Š0.52 D, P = .035). In terms of refractive stability, between 1 and 3 months, both groups had mean absolute change of SE of around 0.25 D. Between 3 and 6 months, preoperative low-to-moderate myopia group had significantly less absolute change of SE compared to high myopia group (0.07 vs 0.23 D, P = .003). More eyes with preoperative high myopia changed SE by more than 0.25 D than those with low-to-moderate myopia between 3 and 6 months (32.0% vs 5.6%, P = .057).In conclusion, LASEK with MMC is more unpredictable and unstable in correction of high myopia than low-to-moderate myopia. The refractive outcome of most low-to-moderate myopia correction stabilizes at 3 months. Stability is not achieved until after 6 months in high myopia correction.